Serum Albumin Levels Are Associated with Total Brain and Hippocampal Volume but Not with White Matter Lesion Volume in Older Japanese Adults Without Cognitive Decline: A Cross-Sectional Study

Background/Objectives: Serum albumin has antioxidant, anti-inflammatory, and antithrombotic properties and reflects nutritional status. Hypoalbuminemia is linked to cognitive decline and frailty. However, the relationship between serum albumin levels and brain structural changes in older adults remains unclear. We aimed to examine the associations between serum albumin levels and total brain, hippocampal, and white matter lesion volumes in cognitively normal, community-dwelling older Japanese adults, accounting for frailty status. Methods: In this cross-sectional study, 7266 participants aged ≥65 years without cognitive decline were included. Serum albumin levels, maximum handgrip strength, and usual gait speed were measured in all participants. Brain magnetic resonance imaging scans were used to evaluate total brain, hippocampal, and white matter lesion volumes. Results: Lower serum albumin levels were significantly associated with smaller total brain and hippocampal volumes after multivariable adjustment (both p for trend < 0.001; partial η2 = 0.005), but not with white matter lesion volumes (p for trend = 0.24; partial η2 = 0.001). In subgroup analyses stratified by frailty status, no significant heterogeneity in the associations between serum albumin levels and each brain volume was observed between groups defined by maximum handgrip strength or usual gait speed. Conclusions: Lower serum albumin levels are associated with smaller total brain and hippocampal volumes in cognitively normal, community-dwelling older Japanese adults, irrespective of frailty status. Serum albumin may serve as a clinically accessible marker of nutritional conditions in relation to these brain structures in older adults.